A major goal in achieving better global health is the development of a vaccine for tuberculosis, a latent bacterial infection found in about 27% of the world’s population. When the infection becomes active, e.g., when one’s immune system is weak (currently about 20% of all cases) and if it is untreated with antibiotics, it is fatal and about 1.4 million people die of TB annually (Global Health Primer TB). A vaccine is needed to replace the current, partially effective vaccine, called bacille Calmette-Guérin or BCG, that was invented in the early 1900s and of which more than 100 million doses are now administered each year, primarily in countries where TB is endemic like India, Pakistan, Russia, and Brazil. While BCG will prevent TB infection of infants, but with an efficacy of 50-80% (Wikipedia article), it does not prevent primary infection or conversion from the latent to active state in adolescents and adults. In addition, immune-compromised patients (e.g., as in HIV/AIDS) do not respond well to treatment with antibiotics and strains of TB resistant to some or all antibiotics are emerging (WHO TB Fact Sheet).
The global health community, academic institutions, and the biotech/pharma industry have responded to this need over the past years and in 2001 a modest $100 million was spent to develop a new vaccine (the total TB R and D spending was about $500 million, WHO TB background paper). This effort has resulted in about two dozen vaccine candidates in the pipeline with one in Phase III and seven in Phase II trials that are aimed at either preventing infection, stopping conversion, or eliminating infection (Global Health Primer TB). One candidate, VPM1002, achieved a major business milestone in its development last week when it was licensed to the Serum Institute of India (SII), a major manufacturer of vaccines for the developing/emerging market countries (Fiercevaccines press release). VPM1002 is based on an approach invented at the Max Planck Institute for Infection Biology of Berlin, in which the BCG vaccine (which is actually a weakened form of a mycobacteria related to the TB bug that infects cows) is made more effective by the addition of two genetic modifications to make the vaccine more “visible” to the immune system (for more on the technology, see Velmurugan t al. 2013).
The deal was clearly a major commitment by SII which will still need to scale up and get approved a GMP manufacturing process in parallel with conducting several Phase III-level trials, at a cost tens of millions of dollars at least. SII may also need to secure country-by-country regulatory approval for adult use. SII is a WHO prequalified vendor for sale to the WHO’s Expanded Programme on Immunization which promotes and subsidizes childhood vaccinations and already is a supplier of its version of BCG called Tubervac. The parties did not provide any information on the terms of the deal, so it is not clear what SII’s upfront financial commitment was. Nor it is clear how SII valued the candidate; the Phase II study was completed last October, but the results have not been reported according to the NIH trial tracking system (VPM1002 status). SII must have ranked VPM1002 highly since five of the other candidate vaccines at Phase II/III have no major manufacturing partners. One detail of the license was suggested in that the licensor’s CEO implied that SII is committed to the accessibility and affordability of the final product: “Only an experienced and specialized developer and global player like Serum is able to ensure that the vaccine will be made available to people everywhere at a fair price.”
I was also interested in how VPM1002 progressed to Phase II since the preclinical and early clinical studies likely required millions of dollars and substantial product development experience. According to the press release, Vakzine Projekt Management GmbH, a private company in Hannover, Germany (VPM) granted the license to SII after having obtained the rights from the Max Plank Institute’s tech transfer group. But my poking about the VPM website and the web did not yield useful information. VPM, founded in 2002 as a spin-out from another German research institute, the Helmholtz Centre for Infection Research, calls itself a fee-for-service consultancy and a speculative product developer: “VPM offers tailor-made consultancy and services based on in-depth experience in development of biopharmaceutical candidates. In addition, VPM acquires promising candidates from academic research and develops them in cooperation with a pool of partners to products with a high value potential” (VPM Company), but I wondered how the cash flow from the former could support the latter and doubted that the customers or licensees provided substantial capital. Three “shareholders” are listed by VPM, one a tech transfer company for German academic life sciences institutions, one the donor group for the Helmholtz Center, and the last, an individual. It is possible that VPM funds itself through license fees, and it claims that three of its five products have been licensed, but I could find substantiation for only one. The “CMV dense body technology project” was licensed to small German company earlier this year (Cvec press release). I suspected VPM receives a government or foundation subsidy, but found none. I was also mystified by VPM’s relative lack of product development experience; other than the CEO, none of the management seemed to have taken a product through to launch. But perhaps if I had kept up my study of German, I could be better informed. In any case, congrats to VPM and I look forward to learning more about their business model and the progress of VPM1002.
Readers with good memories may recall that I wrote a post on my favored TB vaccine candidate in June, 2010 (“Una Sorpresa Prometedora”). RUTI, a therapeutic vaccine being developed by Archivel Farma of Spain, has the potential to reduce the time of therapy from months to days and had completed a Phase I trial in 2010. Since then, however, news has been sparse. According to Clinicaltrials.gov, the Phase II trial was completed in January, 2012, but no results were reported (RUTI status). In general, no news on a candidate’s progress is not good news.